Why do we give Corticosteroids during Septic Shock?

Whether you're a med student, intern, resident, or nurse, you've wondered why in the world we give patients who are in septic shock stress dose steroids. This article breaks down in a not-so-easy to understand fashion of the nitty details that are too complex for my post-night shift brain to digest.

The powers that be in Critical Care, SCCM and ESICM, got together for this review with some big guns in the field to write this review discussing Critical Illness-related corticosteroid insufficiency.

Link to Abstract

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Annane D, Pastores SM, Arlt W, Balk RA, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper MS, Marik PE, et al.: Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 43(12):1781–1792, 2017.

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Cortisol Levels: Check prior to SDS in Septic Shock?

Your patient is in septic shock. They've gotten the correct source control, antibiotics, fluids, vasopressors. They remain hypotensive. Getting worse, actually. Could they have relative adrenal insufficiency or one of these fancy-termed conditions such as "critical illness-related corticosteroid insufficiency" (CIRCI)?

Should you check a cortisol level to find out or just start stress dose steroids?

In my practice, I do not check cortisol levels. No need to stick the patient for more blood. No need to waste any additional money for lab tests. No need to delay care in waiting for a lab result. Once the norepinephrine dose starts creeping up, I order stress dose steroids (as well as vitamin c and thiamine at the time of this writing). This is all my medical opinion and not advice, in case you didn't know.

The most recent trials on stress dose steroids do not check cortisol levels, so why should you? I tried to dig deeper into this point as I cannot get others to stop checking random cortisol levels on their critically ill patients. But why? There's no diagnostic consensus about the appropriate cortisol level for patients in septic shock. In addition to that, there's data that states that "both cortisol and synthetic ACTH challenge assays are unreliable in critically ill patients". So then why do we keep doing it?

Is there something out there that I don't know and you all can provide me with insight on? I'm looking for help on this.

A hat tip to the author. 

Reddy, Pramod. Diagnosis and Management of Adrenal Insufficiency in Hospitalized Patients. American Journal of Therapeutics, 2019. E-pub ahead of print.

Link to Article

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IV Vitamin C in Sepsis: It Should Help Decrease Vasopressor Doses and Duration

The VITAMINS trial didn’t pan out was not a positive study as it was conducted. I’ve already provided my take on that with my main argument being that they took too long to initiate the study drug (median time >25 hours, not including the time to arrive in the ICU). Sepsis management is expedient, you and I see it every day. Waiting over a day is not being expedient.

I’m seeing a benefit in my clinical practice, as admittedly worthless as my opinion is on the grand scheme of evidence. But when something doesn’t make sense from a results standpoint, you need to go back to the basics and wonder what happened.

Here are some things we absolutely know: 88% of patients in septic shock have hypovitaminosis C and 38% of septic shock patients have severe vitamin C deficiency. What many of you may not know, and I’m here to help you understand why I’m so surprised by the findings of the VITAMINS trial, is that vitamin c is a co-factor to the creation of endogenous catecholamines. That means that without vitamin c, your body isn’t going to produce the appropriate amounts of dopamine, norepinephrine, and epinephrine. It also is necessary for the production of vasopressin. It’s as simple as that. 38% of people will not produce appropriate endogenous catecholamines. The fact that administering exogenous vitamin c did not decrease time that the patients were receiving vasopressors in the study makes me wonder why. I am aware that there was a delay of >24 hours to start the therapies in the study but is there more I'm missing. Hopefully you can take some basic biochem away from this post as to why it should work (although it didn't in the study).

A 🎩 tip to the authors.

-EJ




Link to Article

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Carr, A.C.; Shaw, G.M.; Fowler, A.A.; Natarajan, R. Ascorbate-dependent vasopressor synthesis: A rationale for vitamin C administration in severe sepsis and septic shock? Crit. Care 2015, 19, e418.

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VITAMINS Trial: Timing was overlooked

You all know my bias. It shouldn't be a surprise given my body of work: I wanted this to be a positive study. I wanted patients to benefit from this therapy and SURVIVE. I cannot understand the vitriol I have received in my direct messages when I shared my initial take on the study. I’m prepared to deal with more. Bring it!

Ultimately, there's no difference in the the endpoints, whether primary or secondary. No need to go through them in depth. That’s what the data says, that’s what the study concluded. Hat tip to the authors. It is what it is. I can agree with their conclusions based on the study conducted. But clinicians should not take the study as the end of HAT therapy. It would be scientifically irresponsible to do so. The study had a fatal flaw that doomed it from the beginning. Let me explain why. I practice real world medicine. I am not a trialist. I do the best I can every day with what I have.

Here's a take on how I care for septic shock patients for some perspective. There are plenty of nurses and physicians who work with me currently and have worked with me in the past following along on IG who can vouch for my style of practicing medicine.

This is NOT MEDICAL ADVICE. Do not do what I do because I say so. This post is not all 100% all inclusive for every nuisance. Every pt is different. That is your disclaimer.

1. I get a call from a colleague: ED physician, hospitalist, or surgeon regarding a patient who is in septic shock. At this point they have already gotten antibiotics and fluids bc everyone is excellent at this.
2. I go see the patient IMMEDIATELY
3. I assess, as quickly as possible with my limited tools a guesstimate on their fluid status
4. I start vasopressors EARLY while fluid resuscitating
5. pt arrives in the ICU, central line placed, arterial line placed, EV1000 hooked up.
6. I camp out at the nurses station next to the patient with them in my line of sight.
7. I watch how the patient behaves to my interventions, how the vasopressors go up, if they go up
8. As the vasopressor requirement increases, says NE around 10mcg, I start feeling uneasy. Especially how quickly their requirement increases.
9. I pull the trigger after 10-15mcg of NE to start vasopressin, hydrocortisone 50mg IV q6h, vitamin C 1500mg IV q6h and thiamine 200mg IV q12hours. I hit click, click, click, click, on an order set I created for myself on my EMR.
10. I keep on monitoring the patient closely to assess their response and provide additional fluids and learn more about their physiology.
Thing I do on the side: airway, bedside echo, talk to family and patient, management of other sick patients happen in this time period as needed. This post is not all-inclusive.

Needless to say, all of this happens WITHIN 6 HOURS. One has a general idea, within 6 hours of the patient being in septic shock, a pathology that has a 25-40% mortality rate depending on the study, what is the likelihood of the patient turning the corner.

What can we all agree on regarding management for sepsis: early antibiotics make a difference. Early source control makes a difference. Early fluids are better than late fluids. Early vasopressor administration is showing to be better than late (data for that coming soon).

Here’s my main problem with the study:
- Time for patients to get randomized: I CAN'T FIND THIS DATA
- Time from ICU admission to randomization: 13.7 hours (IQR 7.1-19.3 hrs).
- Median time for patients to receive study study from randomization: 12.1 hours (IQR, 5.7-19 hours).
13.7 + 12.1 = 25.8 hours PLUS time for patients to get randomized!
For those who don't know what IQR means: click here

Why in the world did they take so long to start the study drugs?

That's my problem with the study. My larger problem with the study is the fact that, since it was published in JAMA, a very high impact factor journal, clinicians are going to take it as gospel and dismiss the therapy entirely. If they would have provided the study drugs appropriately, there may have been a difference in outcomes. Since they didn't, patients who could have potentially benefitted will not.
Or maybe I'm just wrong.

-EJ



Link to FULL FREE ARTICLE


Fujii T, Luethi N, Young PJ, et al. Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial. JAMA. Published online January 17, 2020.

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Stress dose steroids for septic shock: bolus dosing or continuous infusion

This study published just this month, November 2019, suggests that providing bolus dosing of hydrocortisone, 50mg IV every 6 hours shortens the time a patient needs to be on vasopressors compared to 200mg IV through a continuous infusion every day.

Stress dose steroids are clearly in my armamentarium in the treatment of septic shock. I tend to reach for them when I’m starting my second vasopressors, usually Vasopressin when the norepinephrine hits around 10-15mcg. I also ready for the vitamin C and thiamine at that point, too. Actually, I have a quick little bundle in the EMR where I just check off all these goodies. Sometimes I stray in different directions, of course. Every patient is different and this is not a recommendation on how you should practice. I haven’t gotten on the fludrocortisone train yet, have you?

Either way, the shock reversal is faster with the bolus dosing. This should make all my nurse followers happy as they won’t have a channel and lumen bogged down with this medication and all the compatibility questions that arise with it. Whether bolus or continuous dosing you won’t see a difference in mortality, ventilator days, adverse effects, length of stay, etc.

Also not yet another study where they don’t check cortisol levels before initiating this treatment. I’m not a fan of checking cortisol levels myself. I see it done and I ask, why?

A 🎩 tip to the authors.

-EJ

Link to FULL FREE Article

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Corticosteroids and GI bleeds: Do We Really Need To Worry?

Link to Abstract

Butler E, Møller MH, Cook O, et al. The effect of systemic corticosteroids on the incidence of gastrointestinal bleeding in critically ill adults: a systematic review with meta-analysis. Intensive Care Med. 2019;45(11):1540–1549. doi:10.1007/s00134-019-05754-3

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation

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Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.